Ambrisentan and Tadalafil Combination Therapy Appropriate for CTD-PAH - Pulmonology Advisor

Posted: 06 Apr 2020 08:15 AM PDT

Combination therapy is appropriate for patients with typical pulmonary arterial hypertension (PAH) categorized as low and intermediate risk at baseline, while high-risk patients could possibly be considered for more advanced therapy, according to study results published in the Annals of the Rheumatic Diseases.¹

Connective tissue disease-associated PAH (CTD-PAH) is the second most common etiology of PAH and has the most severe disease characteristics and the highest mortality of all PAH subgroups.¹ The Ambrisentan and Tadalafil in Patients with PAH study (AMBITION; ClinicalTrials.gov Identifier: NCT01178073) demonstrated that patients with CTD-PAH benefited from initial combination therapy with ambrisentan plus tadalafil compared with either agent alone when patients with risk factors for left heart disease were excluded.²

Researchers conducted a post hoc subgroup analysis of the AMBITION modified intention-to-treat CTD-PAH population to assess the relationship between baseline characteristics and outcome and evaluated the utility of an abbreviated, 3-parameter noninvasive risk stratification score in predicting outcomes in patients with CTD-PAH.¹

This analysis included 216 patients (combination therapy, n=117; monotherapy, n=99), and they found that the risk for clinical failure was lower with combination therapy vs monotherapy, specifically 51.7% lower in the CTD-PAH population (hazard ratio [HR], 0.48; 95% CI, 0.28%-0.81%) and 53.7% in the systemic sclerosis-PAH population (HR, 0.46; 95% CI, 0.24%-0.89%). The risk for clinical failure was lower with combination therapy vs monotherapy in the baseline low-risk group, baseline intermediate-risk group, and in the week 16 low-risk group.

"In patients with CTD-PAH, the risk of clinical failure was lower with combination therapy versus monotherapy, particularly in those with baseline hemodynamic parameters characteristic of typical PAH, without features of left heart disease and/or restrictive lung disease,"¹ the investigators wrote. "A simplified risk stratification score at baseline may help inform disease management in patients with CTD-PAH, but further studies with larger patient populations are required."

Disclosure: This clinical trial was supported by GlaxoSmithKline and Gilead Sciences, Inc. Please see the original reference for a full list of authors' disclosures.

References

1. Kuwana M, Blair C, Takahashi T, Langley J, Coghlan JG. Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis [published online March 11, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216274

2. Galiè N, Barberà JA, Frost AE, et al; for the AMBITION Investigators. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373:834-844.

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Pulmonary Arterial Hypertension Pulmonary Hypertension

Inoperable CTEPH Safely Treated Using Balloon Pulmonary Angioplasty - Pulmonary Hypertension News

Posted: 06 Apr 2020 06:00 AM PDT

Balloon pulmonary angioplasty (BPA) is a safe and effective, minimally invasive treatment for people with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), according to a study from the U.K.

The study describes the treatment of the first group of CTEPH patients to be treated with BPA.

"Balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: the UK experience," was published in the journal openheart.

CTEPH is a rare form of pulmonary hypertension, characterized by high blood pressure in the arteries that supply blood to the lungs. The disease is caused by blood clots that obstruct these pulmonary arteries.

Pulmonary endarterectomy (PEA) is an established treatment to remove blood clots, and the recommended treatment approach for CTEPH patients. But PEA is a major surgical procedure, with an intraoperative mortality rate of around 2.2%, and a major complication rate of nearly 50%.

An estimated 40% of CTEPH patients are also ineligible for the PEA procedure, and 20% of patients undergoing PEA may still be left with only partial lung function. Inoperable CTEPH patients tend to have less favorable prognoses, and higher symptom burden.

BPA involves placing balloon catheters into pulmonary vessels, then inflating them to unblock the vessel and restore healthy blood flow.

Analyses of past BPA use suggest that the procedure is equivalent to PEA, but no randomized, controlled trial data have been published to date.

Researchers with the Royal Papworth Hospital evaluated the efficacy and outcomes of BPA in 30 inoperable CTEPH patients (22 males; mean age of 63.5) treated between October 2015 and April 2018. The national BPA service in the U.K. opened in October 2015.

Patients underwent an average of three BPA treatment cycles at one-month intervals.

Results showed that each BPA course improved all hemodynamic measures, in particular the mean pulmonary arterial pressure (mPAP; mean reduction of 44.7 to 34.4 mm Hg at three months post-procedure) and pulmonary vascular resistance (PVR; mean reduction of 663 to 436 dyn.s.cm^-5). Both mPAP and PVR are measures of how hard the heart must work to pump blood through pulmonary vessels.

A modest improvement in cardiac output (the amount of blood the heart pumps in one minute) was also observed after BPA. Such improvement resulted in better exercise capacity and symptom scores, as measured by the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).

Patients also showed clear evidence of reduced right heart strain, and beneficial changes in the size and workings of the right ventricle.

Importantly, researchers found that BPA's meaningful improvements in clinical measurements translated into symptomatic and quality-of-life benefits for the patients.

No deaths or life-threatening complications were reported, and no one required intensive care or emergency intubation.

Complications that did occur were deemed mild to moderate (10.5% of the cases). These consisted of access site bruising, acute lung injuries, and lung reperfusion edema (fluid retention often seen in lung transplants).

Based on the results, researchers concluded that BPA "is safe and effective in treating inoperable CTEPH with clinically meaningful improvements in haemodynamics, exercise capacity, ventilatory efficiency, and RV [right ventricle] dimensions that translate into symptomatic benefit and improved QoL [quality of life] for patients," they wrote.

These results also led them to speculate that BPA may be more effective than medications in treating CTEPH patients. However, the researchers noted that a first clinical trial testing BPA versus riociguat (marketed as Adempas, by Bayer) has not published its results (the RACE trial, NCT02634203). More studies are needed.

"Further work is also required to explore the nuances of the optimal BPA strategy," the team added.

Author Details

Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.

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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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